This proposal is a renewal of an ongoing collaborative program between investigators at the Massachusetts Institute of Technology, the New England Eye Center (NEEC) and the University of Pittsburgh Medical Center Eye Center (UPMC). This program is a multidisciplinary effort which integrates fundamental studies, technology development and clinical studies. The specific aims are: Aim 1. Develop new ultrahigh speed OCT technology at 800nm and 1050nm wavelengths We will develop new OCT technology for clinical studies at NEEC and UPMC. We propose to develop advanced OCT technologies which increase imaging speeds and resolutions to enable rapid volumetric imaging and mapping of detailed retinal architectural morphology such as the photoreceptor rod and cone outer segments, the Bruch's membrane/retinal pigment epithelium complex and drusen morphology. We will also develop long wavelength OCT which enables imaging of the choroid and internal structure of the optic nerve head. Aim 2. Develop spectroscopic OCT for functional imaging We will investigate and validate spectroscopic OCT imaging in the visible wavelength regime to measure blood oxygenation in retinal vasculature and macular pigment concentration. Studies will be performed in animal models, ex vivo retinal preparations and in human subjects. These new techniques will develop integrated functional and structural OCT imaging and have broad applications to fundamental research. Aim 3. Develop new techniques for adaptive optics enhanced OCT We will develop an AO-OCT system for clinical use at NEEC. We also propose to develop AO-OCT technology for small animals to achieve cellular level resolution in rats and mice. The improved transverse resolution of AO-OCT combined with the ultrahigh axial resolutions and speeds of SD/FD-OCT will enable visualization and quantification of small retinal features, such as alterations of the rod photoreceptor mosaic and RPE which could be markers of disease. Aim 4. Perform clinical studies to investigate advanced OCT for identifying markers of disease The goal of this aim is to identify disease markers for AMD and glaucoma using advanced OCT technology, as well as to compare the clinical performance of OCT at 1050nm and 800nm. We will perform cross-sectional and longitudinal studies in patients with AMD to identify markers for disease and predictors of disease progression. Studies in glaucoma will investigate the role of ultrahigh resolution versus ultrahigh speed for improving reproducibility of morphometric measurements as well as investigate potential new markers for disease including changes in the lamina cribrosa and intraretinal vasculature. This research serves the dual role of developing the next generation of OCT technologies and validating OCT applications for the assessment of AMD and glaucoma.